Acute demyelinating
encephalomyelitis (ADEM) is a disease of prepubertal
children, typically occurring one to three weeks after a
clearly identifiable febrile prodromal illness of viral
infections and occasionally bacterial infections or
immunization [1,2]. Most patients of ADEM recover fully,
usually without treatment. Post-malarial ADEM usually
occurs after recovery from the severe falciparum malaria
and is considered to be an immune-mediated neurological
complication [3-8]. However, we could not find any
report of ADEM following malaria in children.
Case Report
A 12-year-old female child was
admitted with complaints of high-grade fever,
generalized tonic-clonic convulsions and altered
consciousness. She was admitted three weeks prior also
for high grade fever, headache and vomiting for three
days and an episode of generalized convulsions and
clouding of consciousness on the day of admission. Her
laboratory examinations revealed anemia (6.5 mg/dL),
mild thrombocytopenia (34000/mm3)
and Plasmodium falciparum infection with 13%
parasitemia. She was treated with intravenous quinine,
doxycline, packed red cell transfusions, along with
supportive therapy. On day, 2, patient regained
consciousness with no further convulsions. On day 4,
there was complete resolution of fever with clearance of
parasitemia and she was discharged on day 5. Sixteen
days after discharge, patient again developed headache,
confusion progressing to clouding of consciousness, and
generalized convulsions leading to another
hospitalization. On admission, patient was
hemodynamically stable with Glasgow coma scale of
E3M5V2. There were no meningeal signs, and no cranial
nerve palsy. Deep tendon reflexes and superficial
reflexes were absent, tone was decreased with positive
Babinski’s sign. Rest of the systemic examination was
normal.
Routine blood investigations
including complete blood count, blood sugar, serum
electrolytes, and renal and liver function tests were
within normal limits except mild elevation in liver
enzymes. Repeated blood smears were negative for
malarial parasites. CSF examination showed normal sugar
(57 mg/dL), protein (11.2 mg/dL), and total cells (5,
all lymphocytes). MRI brain revealed asymmetrical
hyperintense signals on T2 and Diffusion weighted images
(DWI) involving bilateral periventricular white matter,
centrum semiovale and genu of corpus callosum. On the
basis of MRI findings, diagnosis of ADEM was made and
intravenous methylprednisolone therapy was initiated.
Patient showed dramatic response to above therapy and on
day 3, patient regained consciousness, started moving
limbs spontaneously but could not speak. On day 5, she
was conscious and oriented, power was normal but motor
aphasia was still present. Methylprednisolone was
continued for 5 days and then replaced with oral
prednisolone. On day 8, speech output started showing
improvement and by day 13 of admission, she became
neurologically normal and was discharged. Her repeat MRI
brain, done after 3 weeks, showed resolution of changes
seen in previous MRI. After three months of follow up,
patients is normal with no neurological deficits.
Discussion
ADEM has been reported following
P. falciparum infection in adults [3-7]. Etiology of
ADEM following malaria remains unclear but seems to be
immunologically mediated, the mechanism supported by
latency period between falciparum infection and
the onset of ADEM as well as rapid response to steroid
therapy [4,7]. Index case also showed improvement after
steroid therapy with resolution of MRI changes on repeat
imaging study.
Studies have shown plasmodium
infection induced suppression of both humoral and
cellular immunity, leading to superinfection with other
microorganisms [6]. This lag in immunologic improvement
might be seen even after clinical recovery from malaria,
predisposing them to the development of ADEM. Most of
the patients with ADEM show spontaneous and favourable
recovery. In mild cases, symptomatic treatment is
usually sufficient, but in severe cases, corticosteroids
can help limit brain inflammation. As in our case and
case reported by Sharma, et al. [4], patients
received steroids, while few other cases improved
without steroid therapy [5,6]. Signs of recovery can be
seen within days, but complete resolution usually takes
weeks or months [1,2].
The present case reiterates the
importance of post-malarial neurological complications,
which one should keep in mind especially after clinical
recovery from malaria. A few patients may experience
neurological symptoms after complete recovery from
falciparum infection, termed as post-malaria
neurological syndrome (PMNS). PMNS patients typically
have negative blood films at the time of onset,
distinguishing it from cerebral malaria, which occurs
during parasitemia [8,9]. Overall incidence of PMNS was
estimated to be 0.7-1.8 per 1000, with symptoms
occurring within 2 months after malarial episode [9].
According to severity of symptoms,
Schnorf, et al. [10] classified PMNS into three
subtypes: (i) Mild and localized encephalopathy,
characterised by isolated cerebellar ataxia or postural
tremor; (ii) Diffuse but relatively mild
self-limiting encephalopathy causing acute confusion
with or without convulsions; and (iii) Severe
generalized and progressive encephalopathy,
characterised by motor aphasia, generalised myoclonus,
postural tremor, and cerebellar ataxia, resembling ADEM.
No clear demarcation line can be laid
down between PMNS and ADEM due to striking similarities
between these two e.g. latency period, multifocal
neurological deficits, response to steroids, and good
prognosis. However, in PMNS, brain MRI can be normal or
show non-specific hyperintensity as against the
characteristic changes of ADEM that include perivenular
inflammation with surrounding demyelinization and
diffuse or scattered hyperintensity in the white matter
of brain or spinal cord. ADEM also bears clinical and
pathological resemblance with multiple sclerosis and
initial differentiation can be difficult, but later in
the course these two can be distinguished on the basis
of clinical course of disease, lack of relapses, and
resolution of lesions on repeat MRI [1,2].
Contributors: SG:
Acquisition of data, patient management, and
literature review; AA: Concept, drafting the
article, manuscript review, manuscript editing, revising
the article critically for important intellectual
content; AA will act as guarantor. Both the authors
approved the final manuscript.
Funding: None; Competing
interests: None stated.
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